Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor shown clinically to lower plasma cholesterol levels. Lomitapide, also known as N-(2,2,2-Trifluorethyl)-9-[4-[4-[[[4′-(trifluoromethyl)[1,1′biphenyl]-2-Y1]carbonyl]amino]-1-piperidinyl]butyl]9H-fluorene-9-carboxamide, is approved to treat homozygous familial hypercholesterolemia (HoFH), a serious genetic disorder which, if left untreated, leads to the development of atherosclerosis.
However, lomitapide (e.g., a lomitapide mesylate salt) can contain process impurities, including unreacted starting materials, chemical derivatives of impurities contained in starting materials, synthetic by-products, and degradation products. Such impurities present in a lomitapide composition can arise, e.g., from degradation, including during storage or during the manufacturing process, including the chemical synthesis.
In addition to stability, which may be a factor in the shelf life of lomitapide, the purity of lomitapide produced in the commercial manufacturing process is an important condition for commercialization. Impurities introduced during commercial manufacturing processes must be limited to small amounts, and are preferably substantially absent.
At certain stages during processing of lomitapide, it can be analyzed for purity, e.g., by high performance liquid chromatography (HPLC) or thin layer chromatography (TLC), to determine if it is suitable for continued processing and, ultimately, for use in a pharmaceutical product. In the United States, the Food and Drug Administration guidelines recommend that the amounts of some impurities be limited to less than, for example, 0.1 percent.
Therefore, a continuing need exists to identify potential lomitapide impurities and to develop readily usable identification methods to determine the presence and/or quantity of a lomitapide impurity in a lomitapide composition.